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Updated: Feb 28, 2026
Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
Biochemical and Pharmacological Characterization of a Mice Model of Complex Regional Pain Syndrome
Vaskar Das1, Jeffrey S Kroin, Mario Moric
1From the Department of Anesthesiology, Rush University Medical Center, Chicago, IL.
Background And Objectives:
Complex regional pain syndrome is a challenging disease to treat. Recently, a mouse fracture model of complex regional pain syndrome has been developed that has many signs of the clinical syndrome. However, many aspects of the sensory neuron biochemistry and behavioral and pharmacological characterization of this model remain to be clarified.
Methods:
Mice were randomly assigned to fracture/cast or control (naive) groups. Fracture/cast mice underwent a closed distal tibia facture, with hindlimb wrapped in casting tape for 3 weeks. After cast removal, mice were tested for mechanical allodynia, burrowing behavior, and motor ability over a 12-week period. Protein immunohistochemistry was performed for substance P, calcitonin gene-related peptide, tropomyosin receptor kinase A, nerve growth factor, Nav1.7, and transient receptor potential cation-channel V1, colocalized in neurons, in the ipsilateral lumbar dorsal root ganglia (DRGs). Analgesic drugs were tested for pain-relieving efficacy.
Results:
Mechanical allodynia was greater in the ipsilateral hindpaw (P = 0.0002) in the fracture/cast group versus the control group, over the 3- to 12-week period. The amount of burrowing material removed was decreased (P = 0.0026), and there were deficits in spontaneous motor-rearing behavior (P = 0.018). Immunostaining of substance P, calcitonin gene-related peptide, Trk A receptor, nerve growth factor, Nav1.7, and transient receptor potential cation-channel V1 all demonstrated up-regulation in the DRGs of fracture mice versus controls (all P < 0.05). Morphine, pregabalin, ketamine, acetaminophen, and dexamethasone transiently increased force withdrawal thresholds on the ipsilateral (fracture) side and improved burrowing activity after injection (all P < 0.05). Ketorolac improved only burrowing.
Conclusions:
Persistent pain-related behavior was demonstrated in this mouse fracture/cast model with wide-scale DRG up-regulation of pain mediators. Antihyperalgesic drugs reduced mechanical allodynia and improved burrowing.
Insights
This study demonstrates a mouse fracture model exhibiting persistent pain behaviors and biochemical changes. Several drugs effectively reduced pain and improved function in this complex regional pain syndrome model.
Area of Science:
- Neuroscience
- Pain Research
- Animal Models
Background:
- Complex regional pain syndrome (CRPS) presents significant treatment challenges.
- A novel mouse fracture model mimics key CRPS symptoms.
- Further characterization of sensory neuron biochemistry and pharmacology is needed.
Purpose of the Study:
- To characterize the sensory neuron biochemistry and behavioral/pharmacological aspects of a new mouse fracture model of CRPS.
- To assess pain-related behaviors including mechanical allodynia and burrowing.
- To evaluate the efficacy of analgesic drugs in this model.
Main Methods:
- Mice were subjected to a tibia fracture and casting for 3 weeks.
- Behavioral tests included mechanical allodynia, burrowing, and motor activity.
- Immunohistochemistry analyzed dorsal root ganglia (DRGs) for pain mediators (e.g., substance P, CGRP, TrkA, NGF, Nav1.7, TRPV1).
- Analgesic drug efficacy was tested.
Main Results:
- Fracture mice showed increased mechanical allodynia and decreased burrowing/motor activity compared to controls.
- Up-regulation of substance P, CGRP, TrkA, NGF, Nav1.7, and TRPV1 was observed in DRGs of fracture mice.
- Morphine, pregabalin, ketamine, acetaminophen, and dexamethasone improved pain thresholds and burrowing.
- Ketorolac improved burrowing behavior.
Conclusions:
- The mouse fracture model effectively replicates persistent pain behaviors seen in CRPS.
- Widespread upregulation of pain mediators in DRGs supports the model's validity.
- Antihyperalgesic drugs demonstrate therapeutic potential in this CRPS model.
